MicroRNA-493 suppresses cell proliferation and invasion by targeting ZFX in human hepatocellular carcinoma

Cancer Biomark. 2018;22(3):427-434. doi: 10.3233/CBM-171036.

Abstract

Backgrounds: MicroRNAs (miRNAs) are some RNA molecules that negatively regulate gene expression by binding to the 3'-untranslated region (3'-UTR) of target mRNA molecules. The aim of the study is to investigate the clinical role and functional effects of microRNA-493 (miR-493) in human hepatocellular carcinoma (HCC).

Methods: Expression of miR-493 in 58 cases of HCC tissues and adjacent normal tissues was determined by using quantitative real-time PCR (qRT-PCR) analyses. In vitro, cell proliferation and invasion capacity was evaluated by CCK8 assay and trans-well invasion assay. Luciferase reporter assay, western blot and qRT-PCR were used to detect the association between miR-493 expression and zinc finger protein X-linked (ZFX) in HCC.

Results: Expression of miR-493 was significantly downregulated in HCC tissues compared to adjacent normal tissues. Lower miR-493 expression associated with tumor size, vascular invasion and poor overall survival (OS) and disease free survival (DFS) time of HCC patients. In vitro, transfection of miR-493 mimic in HCC cells inhibited cell proliferation and invasion abilities. However, transfection of miR-493 inhibitor in HCC cells had promoting effects. Luciferase reporter assay, qRT-PCR and western blot analysis demonstrated that miR-493 targeting 3'-untranslated region (3'-UTR) of ZFX and overexpression of miR-493 inhibited its expression. Moreover, enforced ZFX expression rescued the effects of miR-493 mimic on cell proliferation and invasion.

Conclusion: MiR-493 functioned as tumor suppressor in HCC cells by regulating ZFX expression. Thus, miR-493 may provide potential value for HCC treatment.

Keywords: MicroRNAs; ZFX; cell invasion; cell proliferation; miR-493.

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Biomarkers, Tumor
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Humans
  • Kruppel-Like Transcription Factors / genetics*
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • RNA Interference
  • Tumor Burden

Substances

  • 3' Untranslated Regions
  • Biomarkers, Tumor
  • Kruppel-Like Transcription Factors
  • MIRN493 microRNA, human
  • MicroRNAs
  • zinc finger protein, X-linked